"Block-and-Lock" Strategy for HIV-1 Treatment

Scientists have for the first time shown that a novel compound effectively suppresses production of the virus in chronically infected cells, and prevents viral rebound, even when those infected cells are subjected to vigorous stimulation.The study was published in the journal Cell Reports.

"No other anti-retroviral used in the clinic today is able to completely suppress viral production in infected cells in vivo," senior author said. "When combining this drug with the standard cocktail of anti-retrovirals used to suppress infection in humanized mouse models of HIV-1 infection, our study found a drastic reduction in virus RNA present--it is really the proof-of-concept for a 'functional cure.'"

This new approach is called "Block-and-Lock"--the approach blocks reactivation of the virus in cells, even during treatment interruptions, and locks HIV into durable state of latency.

Researchers use a derivative of a natural compound called didehydro-Cortistatin A (dCA), which blocks replication in HIV-infected cells by inhibiting the viral transcriptional activator, called Tat, halting viral production, reactivation and replenishment of the latent viral reservoir.

"Combining dCA with anti-retroviral therapy accelerates HIV-1 suppression and prevents viral rebound after treatment interruption, even during strong cellular activation," senior author said. "It's important to note that our study uses the maximum tolerable dose of the drug--with virtually no side effects."

The scientists studied the combination therapy in a mouse model of HIV latency and persistence. Once the combined treatment regimen was halted, viral rebound was delayed up to 19 days, compared with just seven days in mouse models receiving only anti-retroviral treatment.

The animal models were exposed to just a single month of treatment. "That's a relatively short period of time," senior author said. "We think longer treatments will result in longer, or even permanent, rebound delays. The question is how long? We're studying that now."

Because any viral rebound of HIV comes with a host of adverse effects, blocking that rebound would automatically reduce those effects.

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